Studies On Chemical Constituents Of Gentiana Macrophylla And Aglaia Elaeagnoidea And Their Biological Activities

Gentiana macrophylla Pall.is a traditional Chinese medicine with a long history.It has showed extensive biological activites,such as anti-inflammatory,hepatoprotective,choleretic effects,ect.Traditionally,it has been used for the treatment of rheumatic arthritis,hepatitis,and damp-heat jaundice.G.macrophylla contains structurally diverse compounds,including iridoids as the main component,as well as triterpenes,flavonoids,phenylpropanoids,phenolic acid derivatives and other secondary metabolites.Previously,researches on its biological activities were mostly concentrated on the anti-inflammatory,liver protection,and antioxidant activities of iridoids.Aglaia elaeagnoidea(Aglaia)is widely grown in Yunnan,Guangxi,and other southern provinces in China.To date,nearly 300 compounds have been isolated from plants of the genus Aglaia,mainly including flavaglines as the chemical marker,as well as triterpenes,steroids,alkaloids,and sesquiterpenes.In the present study,we focused on the research of 70% ethanol extract of G.macrophylla and 95% ethanol extract of A.elaeagnoidea.The petroleum ether,ethyl acetate,and n-butanol layers were systematically isolated by varieties of column chromatographic methods.The structures were determined by a wide range of spectroscopic techniques,including NMR,HRESI-MS,IR,UV,and ECD spectra.The hepatoprotective and anti-pneumonia effects of some isolated compounds were evaluated.A total of 35 compounds were identified from G.macrophylla,including lignans,iridoids,triterpenes,sesquiterpenes,flavonoids,and other secondary metabolites.Among them,eleven new compounds(1-5,7,12,13,18,20,and 25)were reported,which enriched the chemical composition of G.macrophylla.Eleven compounds(6,11,16,19,28-33,and 35)were firstly found in species of the genus Gentiana,which enriched the chemical diversity of secondary metabolites from this genus.The hepatoprotective effect for compounds 1-11 against D-Gal Ninduced cytotoxity in AML12 cells were tested by MTT method,and silybin(30 μM)was used as the positive control.The result showed that,at the concentration of 30 μM,compounds 1-4,7,8,and 9 showed promising hepatoprotective effects with statistical significance(P < 0.05);Among them,the new compounds 2,3,and 7 showed significant hepatoprotective effects in the same level as that of silybin.G.macrophylla,G.scabra,Gardenia jasminoides,etc.are heatclearing herbs frequently used in the COVID-19 TCM diagnosis and treatment scheme.The main chemical components of these herbs all contain iridoids.The anti-pneumonia activity of iridoids 12-17 were tested by a TNF-α induced A549 cell injury model.The results showed that the new compound 12 could inhibit the expression of proinflammatory factor IL-1β and IL-8,and increase the level of anti-inflammatory cytokine IL-10 in A549 cells at the concentration of 10 μM,which provided evidence for clarifying the anti-pneumonia effective ingredients of G.macrophylla.Phytochemical investigation of the twigs and leaves of A.elaeagnoidea led to the isolation and identification of twenty-one terpenoids,including two cadinene sesquiterpenoids(36 and37),four isodaucane sesquiterpenoids(38-41),one clovane sesquiterpenoid(42),one aromadendrane sesquiterpenoid(43),four cycloartane triterpenoids(44-47),seven dammarane triterpenoid derivatives(48-54),one lupane triterpenoid(55),and one oleanane triterpenoid(56).Among them,seven sesquiterpenoids(36-42)and five triterpenoids(46,47,50,51,and56)were reported for the first time from the genus Aglaia,which might serve as valuable chemotaxonomic markers for A.elaeagnoidea,as they had not been isolated from other Aglaia species.